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Estrogen Receptor-positive Breast CancerPhase 2NCT00602043

F-18 16 Alpha-Fluoroestradiol-Labeled Positron Emission Tomography in Predicting Response to First-Line Hormone Therapy in Patients With Stage IV Breast Cancer

A Phase 2 study testing F-18 16 alpha-fluoroestradiol, fludeoxyglucose F 18 and positron emission tomography in people with Estrogen Receptor-positive Breast Cancer and Progesterone Receptor-negative Breast Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase II trial is studying how well F-18 16 alpha-fluoroestradiol (FES) imaging works in predicting response to first-line hormone therapy in women with hormone receptor-positive metastatic breast cancer. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
F-18 16 alpha-fluoroestradiol, fludeoxyglucose F 18 and positron emission tomography
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
Sep 2008to Sep 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients will have pathologically confirmed invasive breast cancer with clinical, radiographic and/or pathologic evidence of stage IV disease; patients must have tissue blocks available from biopsy of at least one site of metastatic disease and/or from diagnosis of their primary breast cancer
  • Disease may be measurable (by Response Evaluation Criteria in Solid Tumors [RECIST] criteria) or non-measurable but must be present in at least one non-liver site and imageable on FDG PET scan; in patients with non-measurable disease by RECIST criteria, one of the following may be used to assess and follow disease: MUC-1 antigen level (either cancer antigen [CA] 27.29 or carcinoembryonic antigen [CEA]) > 2 x upper limit of normal (ULN), Circulating tumor cell assay > 5, or FDG-PET SUV > 2.5 in purely lytic lesions; elevated tumor markers alone are insufficient
  • No prior endocrine therapy for breast cancer or
  • Off adjuvant endocrine therapy for > 6 months or
  • Greater than 2 years of a single adjuvant endocrine therapy at the time of first recurrence and plan to change to alternate endocrine therapy; use of tamoxifen must be discontinued 6-8 weeks prior to entrance into the study
  • Prior chemotherapy regimens in the adjuvant or neoadjuvant setting are allowed
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  • Women treated with adjuvant LHRH (luteinizing hormone-releasing hormone) analog are eligible
  • Be assessed for menopausal status; for study purposes, postmenopausal is defined as:
  • A prior documented bilateral oophorectomy, or
  • A history of at least 12 months without spontaneous menstrual bleeding, or
  • Age 60 or older with a prior hysterectomy without oophorectomy, or
  • Age less than 60 with a prior hysterectomy without oophorectomy (or in whom the status of the ovaries is unknown), with a documented follicle stimulating hormone (FSH) level demonstrating confirmatory elevation in the postmenopausal range for the lab
  • Premenopausal patients must have a baseline FSH, and estradiol levels to determine menopausal status; measures will be repeated at 3-6 months to confirm menopausal status
  • Patients must be positive for estrogen receptor (ER) and may or may not be positive for progesterone receptor (PgR) by IHC in the primary tumor and/or metastatic site; the pathology report for assay of ER will be reviewed by one of the investigators prior to enrollment, the study pathologist will review the pathology report if necessary for determination of study eligibility
  • Tumor HER2/neu expression must be determined prior to study enrollment; assessment may be by fluorescence in situ hybridization (FISH) assay or by immunohistochemistry (ICC); if determination is intermediate by ICC, FISH must be performed
  • Life expectancy > 16 weeks
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Absolute neutrophil count (ANC) >= 1,000
  • Platelet count >= 50,000
  • Hemoglobin within normal limits (WNL) for the institution
  • Serum creatinine =< 1.5 x institutional ULN (IULN) and estimated creatinine clearance > 50 mL/min using the Cockroft-Gault formula
  • Bilirubin =< 1.5 x ULN
  • Serum glutamic oxaloacetic transaminase (SGOT)/ serum glutamic pyruvate transaminase (SGPT) =< 1.5 x ULN
  • Alkaline phosphatase =< 2.5 x ULN
  • Patients must be planning a course of endocrine therapy with one of the following: tamoxifen +/- ovarian suppression, aromatase inhibitor +/- fulvestrant (with ovarian suppression in pre-menopausal patients) or fulvestrant alone
  • After entry into the study, patients are expected to be followed for at least 6 months after the injection of [^18F] FES
  • Have a negative pregnancy test within 7 days prior to registration if of childbearing potential
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or any other cancer from which the patient has been disease-free for 5 years
  • Be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study-specific screening procedures
  • Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

Who cannot join

  • Patients with a history of prior endocrine therapy for metastatic disease are NOT eligible; adjuvant endocrine therapy for < 2 years total or discontinued less than 6 months before first disease recurrence also excludes the patient
  • Patients with disease in the liver only are NOT eligible for the study
  • Patients who are HER2/neu positive disease and planning to undergo HER2-directed therapy (trastuzumab or lapatinib) are NOT eligible for the study
  • Pregnant or lactating; women of childbearing potential with either a positive or no pregnancy test at baseline are excluded
  • Visceral crisis characterized by rapidly progressive hepatic or lymphangitic lung metastases
  • History of uncontrolled seizures, central nervous system disorders, or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent
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  • Any other life-threatening illness (e.g., serious, uncontrolled concurrent infection or clinically significant cardiac disease - congestive heart failure, symptomatic coronary artery disease, cardiac arrhythmia not well controlled with medication)
  • Unwillingness to give informed consent
  • Medically unstable as judged by the patient's physician
  • Psychological, familial, sociological, or geographical conditions which do not permit compliance with the study protocol
  • Patients with known allergic or hypersensitivity reactions to previously administered radiopharmaceuticals; patients with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator's discretion
  • Patient weight greater than 400 lbs (exceeds weight limit for tomograph table)
  • Uncontrolled diabetes mellitus (fasting glucose > 200 mg/dL)
  • Adult patients who require monitored anesthesia for PET scanning

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Washington Medical Center

    Seattle, Washington, 98195

Other trials in United States

About this study

Official title: A Phase 2 Study of [18F] Fluoroestradiol (FES) as a Marker of Hormone Sensitivity of Metastatic Breast Cancer

This phase II trial is studying how well F-18 16 alpha-fluoroestradiol (FES) imaging works in predicting response to first-line hormone therapy in women with hormone receptor-positive metastatic breast cancer. Diagnostic procedures, such as FES imaging, may help predict how well patients will respond to hormone therapy and may help plan the best treatment.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Estimate the ability of [^18F] FES positron emission tomography (PET) or PET/computed tomography (CT) uptake at the level of standard uptake value (SUV) < 1.5 to predict overall response (OR) to first line endocrine therapy for metastatic breast cancer.

SECONDARY OBJECTIVES:

  1. Evaluate the independent role of [^18F] FES in predicting response and time to progression in patients treated with first-line endocrine therapy for metastatic breast cancer.

II. Examine the role of [^18F] FES in predicting OR or clinical benefit (CB), in concert with tissue assay of levels of estrogen receptor (ER) messenger ribonucleic acid (mRNA) measured using quantitative polymerase chain reaction (PCR), and semi-quantitative interpretation of estrogen receptor (ER), progesterone receptor (PgR), androgen receptor (AR), and human epidermal growth factor-2 (HER2), in addition to serial measures of hormone levels in plasma.

III. Evaluate the relationships among [^18F] FES, semi-quantitative ER from immunohistochemistry (IHC), and ER mRNA as measured by quantitative PCR.

IV. Document the safety profile of [^18F] FES PET in newly diagnosed patients with metastatic breast cancer.

  1. Evaluate FES SUV < 1.5 as the optimal cutpoint for predicting OR to first-line endocrine therapy for metastatic breast cancer.

VI. Estimate the rate of [^18F] FES SUV < 1.5 in newly diagnosed metastatic breast cancer patients planning a course of endocrine therapy.

OUTLINE:

Patients undergo [^18F] FES PET scan. Patients also undergo standard clinical fludeoxyglucose F 18 (FDG)-PET or FDG-PET/CT scan up to 14 days prior to [^18F] FES PET scan.

After completion of study treatment, patients are followed up for at least 6 months.

Being tested
F-18 16 alpha-fluoroestradiol, fludeoxyglucose F 18, positron emission tomography, computed tomography, laboratory biomarker analysis
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • F-18 16 alpha-fluoroestradiolRadiation

    Also called F-18 FES, fluorine-18 16 alpha-fluoroestradiol

    Undergo [^18F] FES PET

  • fludeoxyglucose F 18Radiation

    Also called 18FDG, FDG

    Undergo standard clinical FDG PET/CT

  • positron emission tomographyProcedure or surgery

    Also called FDG-PET, PET, PET scan, tomography, emission computed

    Undergo [^18F] FES PET

  • positron emission tomographyProcedure or surgery

    Also called FDG-PET, PET, PET scan, tomography, emission computed

    Undergo standard clinical FDG PET/CT

  • computed tomographyProcedure or surgery

    Also called tomography, computed

    Undergo standard clinical FDG PET/CT

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00602043
Study groupRoleWhat they receive
Diagnostic (FES)ExperimentalPatients undergo [^18F] FES PET scan. Patients also undergo standard clinical fludeoxyglucose F 18 (FDG)-PET or FDG-PET/CT scan up to 14 days prior to [^18F] FES PET scan.
Receives: Radiation: F-18 16 alpha-fluoroestradiol; Radiation: fludeoxyglucose F 18; Procedure: positron emission tomography; Procedure: computed tomography; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Best Overall Response

    Patients were expected to start endocrine therapy within 2 weeks of the FES PET scan. Response assessment was evaluated at 3 and 6 months. For patients with at least one site of measurable disease [per response evaluation criteria in solid tumors (RECIST, version 1.1)], size-based response criteria were used to assess response.

    For patients without disease evaluable by RECIST 1.1, largely patients with bone-dominant metastatic breast cancer, serial FDG PET scanning was used to determine response. A decline in the FDG PET SUV (standard uptake value) of 30% or more was considered as response and an increase of 20% or more was considered to be progressive disease (PD).

    The initial (baseline) FES uptake was compared to clinical benefit (PD versus other outcome at 6 months).

    Measured: Up to 6 months

Secondary outcomes (3)

  1. Number of Participants With Clinical Benefit

    FES SUV prior to endocrine treatment (dichotomized and as a continuous predictor) will also be tested as predictor of clinical benefit.

    Patients were expected to start endocrine therapy within 2 weeks of the FES PET scan. Response assessment was evaluated at 3 and 6 months.

    The initial (baseline) FES uptake was compared to clinical benefit (PD versus other outcome at 6 months).

    Measured: Up to 6 months

  2. Time to Progression

    FES SUV prior to endocrine treatment (dichotomized and as a continuous predictor) will also be tested as predictor of time to progression. Analysis will be conducted using (respectively) logistic regression and Cox proportional hazards regression. This will include univariate analysis of FES and other predictive measures (ER/PgR expression, serum sex steroid levels), followed by an exploratory multivariate analysis combining FES SUV with other measures showing predictive capability univariate analysis.

    Measured: Up to 6 months

  3. Correlation of FES Uptake With ER Assays

    Graphical and numerical studies of bivariate relationships will be examined, as well as factors (i.e., tumor size, tumor location, patient age) to explain concurrence, lack of concurrence, and sources of measurement error for measurements of ER function.

    Measured: Up to 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jan 2008 (estimated)
  2. Study startSep 2008
  3. Primary completionAug 2011
  4. Study completionSep 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Diagnosis
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00602043
Sponsor's protocol ID
NCI-2009-00270
Other IDs
NCI-2009-00270, IRB #6590, CDR0000584077, UWCC-6590, IRB #6590, 8052
Status last verified
Feb 2020
First submitted
23 Jan 2008
Last updated
19 Feb 2020

Publications

  • Peterson LM, Kurland BF, Schubert EK, Link JM, Gadi VK, Specht JM, Eary JF, Porter P, Shankar LK, Mankoff DA, Linden HM. A phase 2 study of 16alpha-[18F]-fluoro-17beta-estradiol positron emission tomography (FES-PET) as a marker of hormone sensitivity in metastatic breast cancer (MBC). Mol Imaging Biol. 2014 Jun;16(3):431-40. doi: 10.1007/s11307-013-0699-7. Epub 2013 Oct 30.

    PubMed 24170452

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing F-18 16 alpha-fluoroestradiol, fludeoxyglucose F 18 and positron emission tomography in people with Estrogen Receptor-positive Breast Cancer and Progesterone Receptor-negative Breast Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Best Overall Response (time frame: Up to 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00602043, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2020.

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